The blood brain barrier may prevent the achievement and maintenance of effective levels of antineoplastic drugs in the cerebrospinal fluid (CSF) and meninges for treatment of leptomeningeal cancer. We intend to surmount this barrier using continuous intraventricular infusions in ambulatory subjects with a newly developed, totally implanted drug delivery system. It should be possible with this system to maintain high, therapeutic CSF drug levels with concurrent low and non-toxic systemic levels. High sustained CSF drug levels should maximize exposure to meningeal tumor by driving drug into tumor cell layers in the meninges and killing an enlarging portion of the tumor cell population as more cells move into drug sensitive cell cycle phases with increasing time. Phase I pharmacokinetic/toxicologic studies using this system will be performed in Rhesus monkeys and in patients with meningeal cancer. Dichloromethotrexate, fluorodeoxyuridine and cytosine arabinoside (Ara-C) plus thymidine--all pharmacologically rational agents not previously examined for intrathecal utility--will be initially studied in the monkey. Clinical studies will begin with methotrexate and Ara-C, agents with prior intrathecal usage, and then proceed to the drugs coming through preclinical testing. Pharmacokinetic studies will generate a dose rate to CSF level curve for each agent. The ratio of CSF level to concurrent systemic drug level will be determined as one measure of regional selectivity. Duration and level of sustained CSF drug will be correlated with toxicity ascertained systematically by a) clinical examination, b) CSF analyses (cells, protein, glucose), c) pathological examination at necropsy, and by d) brain CT scans (in patients only). The knowledge acquired of the delivery system and of the regional pharmacologic effects of these important anticancer agents should advance the experimental therapeutics of leptomeningeal cancers.